m6A-RNA甲基化在口腔癌及癌前病变中的表达及意义
Expression and significance of m6A-RNA-methylation in oral cancer and precancerous lesion.
作者信息
Qin Zhiming, Bai Jiaying, He Huiying, Li Binbin
机构信息
Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, China.
出版信息
Front Oncol. 2023 Jan 30;13:1013054. doi: 10.3389/fonc.2023.1013054. eCollection 2023.
BACKGROUND
Oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) are a series of related pathologic and molecular events involving simple epithelial hyperplasia, mild to severe dysplasia and canceration. N6-methyladenosine RNA methylation, as the most common modification of both coding mRNA and non-coding ncRNA in eukaryotes, participates in the regulation of the occurrence and development of various malignant tumors in human. However, its role in oral epithelial dysplasia (OED) and OSCC remain unclear.
MATERIALS AND METHODS
In this study, multiple public databases were used for bioinformatics analysis of 23 common m6A methylation regulators in head and neck squamous cell carcinoma (HNSCC). Protein expressions of IGF2BP2 and IGF2BP3 were verified accordingly in clinical cohort samples of OED and OSCC.
RESULTS
Patients with high expression of FTO、HNRNPC、HNRNPA2B1、LRPPRC、IGF2BP1、IGF2BP2、IGF2BP3 had a poor prognosis. IGF2BP2 had a relatively high mutation rate in HNSCC, and its expression was significantly positively correlated with tumor purity, and significantly negatively correlated with the infiltration level of B cells and CD8+T cells. The expression of IGF2BP3 was significantly positively correlated with tumor purity and CD4+T cells. Immunohistochemistrically, the expression of IGF2BP2 and IGF2BP3 in oral simple epithelial hyperplasia, OED and OSCC increased gradually. Both were strongly expressed in OSCC.
CONCLUSION
IGF2BP2 and IGF2BP3 were the potential biological prognostic indicators of OED and OSCC.
背景
口腔潜在恶性疾病（OPMDs）和口腔鳞状细胞癌（OSCC）是一系列相关的病理和分子事件，涉及单纯上皮增生、轻至重度发育异常和癌变。N6-甲基腺苷RNA甲基化作为真核生物中编码mRNA和非编码ncRNA最常见的修饰，参与人类各种恶性肿瘤发生发展的调控。然而，其在口腔上皮发育异常（OED）和OSCC中的作用仍不清楚。
材料与方法
本研究利用多个公共数据库对头颈部鳞状细胞癌（HNSCC）中23种常见的m6A甲基化调节因子进行生物信息学分析。并在OED和OSCC的临床队列样本中相应验证了IGF2BP2和IGF2BP3的蛋白表达。
结果
FTO、HNRNPC、HNRNPA2B1、LRPPRC、IGF2BP1、IGF2BP2、IGF2BP3高表达的患者预后较差。IGF2BP2在HNSCC中具有相对较高的突变率，其表达与肿瘤纯度显著正相关，与B细胞和CD8+T细胞浸润水平显著负相关。IGF2BP3的表达与肿瘤纯度和CD4+T细胞显著正相关。免疫组织化学显示，IGF2BP2和IGF2BP3在口腔单纯上皮增生、OED和OSCC中的表达逐渐增加。二者在OSCC中均高表达。
结论
IGF2BP2和IGF2BP3是OED和OSCC潜在的生物学预后指标。
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